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miR-338-3p Is Down-Regulated by Hepatitis B Virus X and Inhibits Cell Proliferation by Targeting the 3′-UTR Region of CyclinD1

Fu, Xiaoyu, Tan, Deming, Hou, Zhouhua, Hu, Zhiliang, Liu, Guozhen·2012·International Journal of Molecular Sciences
DOI 10.3390/ijms13078514PMC PMC3430248
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Abstract

Hepatitis B virus X protein (HBx) is recognized as an oncogene in hepatocellular carcinoma (HCC). HBx regulates microRNA expression, including down-regulating miR-338-3p in LO2 cells. Here, we investigated miR-338-3p function in HBx-mediated hepatocarcinogenesis. In 23 HBV-infected HCC clinical patient tumor and adjacent non-tumor control tissues, 17 and 19 tumors expressed HBx mRNA and protein, respectively. When considered as a group, HBV-infected HCC tumors had lower miR-338-3p expression than controls; however, miR-338-3p was only significantly down-regulated in HBx-positive tumors, indicating that HBx inversely correlated with miR-338-3p. Functional characterization of miR-338-3p indicated that miR-338-3p mimics inhibited cell proliferation by inducing cell cycle arrest at the G1/S phase as assessed by EdU and cell cycle assays in HBx-expressing LO2 cells. CyclinD1, containing two putative miR-338-3p targets, was confirmed as a direct target using 3′-UTR luciferase reporter assays from cells transfected with mutated binding sites. Mutating the 2397–2403 nt binding site conferred the greatest resistance to miR-338-3p suppression of CyclinD1, indicating that miR-338-3p suppresses CyclinD1 at this site. Overall, this study demonstrates that miR-338-3p inhibits proliferation by regulating CyclinD1, and HBx down-regulates miR-338-3p in HCC. This newly identified miR-338-3p/CyclinD1 interaction provides novel insights into HBx-mediated hepatocarcinogenesis and may facilitate therapeutic development against HCC.

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  • CyclinD1 and associated CDKs may act as a 'switch' in the cell cycle, and their activity is inhibited in terminally differentiated neurons but high in the embryonic nervous system.

    “CyclinD1 and associated CDKs may act as a “switch” in the cell cycle, and their activity is inhibited in terminally differentiated neurons but high in the embryonic nervous system [48–51].”

    From MiR-338-3p regulates neuronal maturation and suppresses glioblastoma proliferation. (2017) · cites this paper as [48]

  • Regulation of CyclinD1 expression has been implicated as a potential mechanism by which miR-338-3p affects cell proliferation.

    “Regulation of CyclinD1 expression has been similarly implicated as a potential mechanism by which miR-338-3p affects cell proliferation [48].”

    From MiR-338-3p regulates neuronal maturation and suppresses glioblastoma proliferation. (2017) · cites this paper as [48]

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Authors
Fu, X., Tan, D., Hou, Z., Hu, Z., & Liu, G.
Affiliations
  • Department of Infectious Disease, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
  • The Second Hospital of Nanjing, Nanjing, Jiangsu, 210000, China
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2012-07-09
Volume
13
Issue
7
Pages
8514-8539
ISSN
1422-0067
DOI
10.3390/ijms13078514
PMC
PMC3430248
Cited by
40
References
0
Language
en
Licence
creativecommons.org/licenses/by/3.0/ (vor)

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